title: A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase.
abstract: Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2-BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.
authors.affiliation: Cell Biology Program, Institut Jacques Monod, UMR 7592 Centre National de la Recherche Scientifique-Université Paris Diderot, 75205 Paris Cedex 13, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bolhy
authors.forename: Imène
authors.initials: I
authors.lastname: Bouhlel
authors.forename: Elisa
authors.initials: E
authors.lastname: Dultz
authors.forename: Tania
authors.initials: T
authors.lastname: Nayak
authors.forename: Michela
authors.initials: M
authors.lastname: Zuccolo
authors.forename: Xavier
authors.initials: X
authors.lastname: Gatti
authors.forename: Richard
authors.initials: R
authors.lastname: Vallee
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
authors.forename: Valérie
authors.initials: V
authors.lastname: Doye
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011418:Prophase; D025941:Protein Interaction Mapping; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D000072159:Dynactin Complex; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C421108:NDEL1 protein, human; C440250:NUP133 protein, human; D028861:Nuclear Pore Complex Proteins; C094772:centromere protein F; D004398:Dyneins